Hope for an ME/CFS Autoimmune Subset: A German Researcher Steps Forward

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@Cort I looked to see if this was already posted and did not see it. If I missed it, I apologize and hoping my post can be linked to the existing thread if there is one.

Excellent article re: Dr. Carmen Scheibenbogen in Germany and what she has found to be an autoimmune subset in ME/CFS (or possibly it's own disease, I don't think we know yet for sure)?

I find Dr. Schiebenbogen's research extremely fascinating and think she is really onto discovering a distinct sub-group or mis-diagnosed group. I match with virtually everything in her research from (initially) mounting a feeble response to EBV, having all of the autoantibodies in her study, having elevated ANA and TPO (thyroid) autoantibodies, and having symptoms like POTS, blood flow abnormalities, lung functioning, muscle weakness, etc.

I never had the opportunity to try immuno-adsorption (IA) but strongly suspect I would be a responder (and then relapse) like the subjects in her study. And I know I cannot be alone in this sub-group!

Scheibenbogen is relatively new to this field, but she’s not new to medical research. A trained oncologist and hematologist as well as a physician and Professor of Immunology in Berlin, her research resume includes over 150 publications dating back 25 years.

Yet she’s very quickly become one of our most prolific researchers. Over the past four years her team has published no less than seven papers, has won two Ramsay Awards, and played a central role in the development of the new European Research collaboration, EUROMENE.

In 2016, figuring that when Rituximab worked in ME/CFS it probably did so by whacking antibody producing B-cells, her group examined antibodies against a variety of receptors that affect blood flow, the autonomic nervous system, etc. They found that about 30% of ME/CFS patients in a large study (n=293) had increased levels of antibodies to adrenergic (B2) and/or muscarinic M3/M4 acetylcholine receptors (M3/M4).

That suggested that the immune systems of a significant subset of ME/CFS patients might be attacking the receptors on cells which regulate blood flow, lung functioning, muscle contractions and attention. Furthermore, the finding (a “remarkable” one they said) that the antibody levels of two receptors correlated with a host of immune factors (immunoglobulin levels, T cell activation, elevated ANA, TPO antibodies) suggested that this subset of ME/CFS patients are suffering from an autoimmune disease. Scheibenbogen has suggested that the kind of ME/CFS you have may be dependent on the kind of autoantibodies present in your system.

Similar antibody findings have been found in a range of diseases (postural tachycardia, regional pain syndrome, Alzheimer’s, Sjogren’s syndrome, asthma) some of which have been associated with ME/CFS. They also noted that immunoadsorption factors that are able to mop up these antibodies had proven to be helpful in some diseases. Two years later they put that idea to the test.

The levels of all four antibodies (B1, B2, M3 and M4) declined after the treatment in all 9 participants. These are good results which are hampered by the small sample size and lack of a placebo control. Through our experiences with Rituximab, Synergy and Mirogabalin we’ve learned how little to trust early results. Still, research has to start somewhere and the results thus far present hope for a significant subset of ME/CFS patients.

The Solve ME/CFS Initiative (SMCI) provides funding to five or so researchers every year in its Ramsay Awards. The Awards are quite competitive with SMCI receiving far more applications than it can fund, but over the past two years the Scheibenbogen group has won two – the only group to do so.

This is one of the first times that I’m aware of that a research group has targeted a subset and dug deeper into it. Scheibenbogen’s focus is clearly good news for people in that subset but it’s also good news for people outside of it. If she’s found a robust subset then it needs to be peeled off from other ME/CFS patients because it’s undoubtedly confounding study results for those patients.

The Simmaron Research Foundation is also working with Dr. Scheibenbogen to identify the subset of Dr. Peterson’s patients who fit the autoimmune profile, and to further characterize the subset from a clinical perspective.

Senior Member

@Cort I looked to see if this was already posted and did not see it. If I missed it, I apologize and hoping my post can be linked to the existing thread if there is one.

Excellent article re: Dr. Carmen Scheibenbogen in Germany and what she has found to be an autoimmune subset in ME/CFS (or possibly it's own disease, I don't think we know yet for sure)?

I find Dr. Schiebenbogen's research extremely fascinating and think she is really onto discovering a distinct sub-group or mis-diagnosed group. I match with virtually everything in her research from (initially) mounting a feeble response to EBV, having all of the autoantibodies in her study, having elevated ANA and TPO (thyroid) autoantibodies, and having symptoms like POTS, blood flow abnormalities, lung functioning, muscle weakness, etc.

according to this paper, vestibular symptoms are common in POTS patients, and according to the paper below, there is a link between vestibular damaged and anti TPO antibodies...So we can guess that either an infectious agent is directly producing both vestibular damages and thyroiditis, either anti TPO ab are linked to other auto-antibodies attacking vestibular system and receptors linked to POTS...

"Conclusion
In euthyroid HashimotoThyroiditis patients, a significant relationship between subclinical vestibular damage and the degree of TPO Ab titre was documented.
This finding suggests that circulating antithyroid autoantibodies may represent a risk factor for developing vestibular dysfunction. An accurate vestibular evaluation of HT patients with or without symptoms is therefore warranted."

Phoenix Rising Founder

[Moderator note: Cort's thread was merged into this thread because they share the same topic.]

From a blog on the Simmaron Research Foundation site.

One of the newer faces to ME/CFS Scheibenbogen has pretty much been tearing it up research wise with 7 papers over the past four years...

Carmen Scheibenbogen MD is another sign that the ME/CFS field is slowly but surely hopefully catching on. Scheibenbogen is relatively new to this field, but she’s not new to medical research. A trained oncologist and hematologist as well as a physician and Professor of Immunology in Berlin, her research resume includes over 150 publications dating back 25 years.

Dr Scheibenbogen has identified what she believes is an autoimmune subset in ME/CFS. (Image from Invest in ME)

In short, she’s a respected and established researcher, and one from Germany to boot. (I can’t remember the last German researcher to take on ME/CFS.) Her path to ME/CFS has not been an easy one. Germany hardly acknowledges ME/CFS as a disease, and doesn’t fund ME/CFS research – if I’m reading her right, there is apparently literally no avenue to apply for ME/CFS research funding there.

Yet she’s very quickly become one of our most prolific researchers. Over the past four years her team has published no less than seven papers, has won two Ramsay Awards, and played a central role in the development of the new European Research collaboration, EUROMENE. Her biosketch lists CFS/ME, Immunodeficiency, and Cancer Immunology as her main research interests.

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@pattismith I am not sure how it all ties together (and I do not really have vestibular symptoms if I am understanding you correctly) but my doctors 100% believe that an infectious agent caused my Hashimoto's Disease (my first official diagnosis along with POTS) following mono, a second virus, and toxic mold/mycotoxin exposure.

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@pibee, what are your thoughts on the research? To me, it seems like if IA or plasmapheresis (PP) immediately helps someone (even if they relapse), that we identified an autoimmune cause. Whether this is a sub-set of ME/CFS or another mis-diagnosed autoimmune disease remains to be seen IMO but I think this preliminary work is really interesting and important.

You are like me with a whole bunch of autoantibodies (although not exactly the same ones) but we overlap re: the Cell Trend and thyroid autoantibodies. Our symptoms are different, though, too, and I have never had hypertension (only hypotension) and we've talked about the other stuff before.

But overall, I am glad that one of the researchers is focusing on autoimmunity and am impressed with her work thus far. I hope she is able to get more funding for future studies.

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I feel like unfortunately there is not enough evidence to point there is B-cells autoimmune subgroup, I am deadly afraid of Rituximab and wont do it.

Wish we could hear impressions from those people who were better after IA. What symptoms got better. PEM? Cognitive?!

My impression is that you Ginger have some similar autoimmune neuro disease along with POTS, so this is why you respond so well to AI treatments. Since my case is classical ME, I am afraid maybe ME symptoms come from viruses or something yet unknown like Cell Danger Response, or T cells autoimmunity.

If I am able to get IA/PP+IVIG, I will do it.

I never had many issues like most ME, until summer 2017 after IV ceftriaxone. First was extremely better and then almost the day it was stopped I got "hits" in head, burning of head, lost ability to learn, do math, before had no limitations to socializing, then started to have sometimes also tiredness after talk, sensitivity to noise, throat pains, lung pains ... it was simply ME progression. Antivirals helped with throat pain, noise sensitivity (both completely gone), the rest is still here.

My feeling is that there is a group of people (myself in this group) who have B-cell autoimmunity. I do not know if we are a sub-group of the same illness or have a different illness. I feel that this type of research will help to figure it out b/c if we have a different illness, they can study us separately which benefits everyone and does not confound the research with people with "true ME" (whatever that will turn out to be). I hope that makes sense! And to your second point, I do not know why, but Rituximab did not scare me and my 5th infusion will be the first week of May.

My impression is that you Ginger have some similar autoimmune neuro disease along with POTS, so this is why you respond so well to AI treatments. Since my case is classical ME, I am afraid maybe ME symptoms come from viruses or something yet unknown like Cell Danger Response, or T cells autoimmunity.

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My feeling is that there is a group of people (myself in this group) who have B-cell autoimmunity. I do not know if we are a sub-group of the same illness or have a different illness. I feel that this type of research will help to figure it out b/c if we have a different illness, they can study us separately which benefits everyone and does not confound the research with people with "true ME" (whatever that will turn out to be). I hope that makes sense! And to your second point, I do not know why, but Rituximab did not scare me and my 5th infusion will be the first week of May.

I do not disagree at all which is why I think figuring out the different sub-groups, or all of these hidden illnesses without names, is so important for future research.

Yes, but even with subsets all of ME subsets by definition have PEM, while you dont. This is why I am afraid to be hopeful because of your success, even though we have so similar labs.

Perhaps CellTrend is because we both have POTS, and your other autoantibodies are linked to your muscle weakness, and I have some other causes of brain problems and PEM, other than CellTrend.

Also, I read a bit about muscarinic acetycholine receptors role in brain. They're linked to psychiatric and cognitive disorders a lot, especially mentioned in Schizophrenia and Alzheimers, and also they found some of these autonatibodies to brain in neuropsychiatric disorders.

So if you have zero brain problems (cognitive or psychiatric) perhaps you dont have blood-brain barrier damage, while I do?!Since majority of my problems are brain related.

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@pibee I agree with everything you said although I wonder if the same autoantibodies could cause a variety of symptoms in different people? If so, could treatments like IVIG etc still be helpful in autoimmunity but for different symptoms?

I always think about @Shawn case who was helped by Rituximab for autoimmunity (like me) even though we had different autoantibodies and different symptoms?

Phoenix Rising Founder

@Cort I looked to see if this was already posted and did not see it. If I missed it, I apologize and hoping my post can be linked to the existing thread if there is one.

Excellent article re: Dr. Carmen Scheibenbogen in Germany and what she has found to be an autoimmune subset in ME/CFS (or possibly it's own disease, I don't think we know yet for sure)?

I find Dr. Schiebenbogen's research extremely fascinating and think she is really onto discovering a distinct sub-group or mis-diagnosed group. I match with virtually everything in her research from (initially) mounting a feeble response to EBV, having all of the autoantibodies in her study, having elevated ANA and TPO (thyroid) autoantibodies, and having symptoms like POTS, blood flow abnormalities, lung functioning, muscle weakness, etc.

I never had the opportunity to try immuno-adsorption (IA) but strongly suspect I would be a responder (and then relapse) like the subjects in her study. And I know I cannot be alone in this sub-group!

You sure sound like you're in that subset! That must feel encouraging. You may be in the first subset validated in ME/CFS...how cool would that be?.

I like the fact that she's got some money from the SMCI to look more deeply into this subset. Given the somewhat similar findings in POTS I would be surprised if she and her subset don't get more funding.

Senior Member

Thanks @Cort and I believe I am in that sub-set but I am unclear if it will ultimately be part of ME/CFS or a totally separate autoimmune disease. I am leaning toward the latter and I am also glad that Dr. Scheibenbogen is interested in studying this further.

Phoenix Rising Founder

Thanks @Cort and I believe I am in that sub-set but I am unclear if it will ultimately be part of ME/CFS or a totally separate autoimmune disease. I am leaning toward the latter and I am also glad that Dr. Scheibenbogen is interested in studying this further.

I'm leaning towards the later too - the first disease to break out of the ME/CFS group. Wouldn't that be something.

I dearly hope other researchers are looking for these antibodies. We need validation from other research groups. I remember some time ago Suzanne Vernon tried to get a grant for a grand autoantibody study - she got buy-in from researchers across the U.S. - a very impressive group - but was, alas , turned down. Now maybe things will be different.

Senior Member

@pibee I agree with everything you said although I wonder if the same autoantibodies could cause a variety of symptoms in different people? If so, could treatments like IVIG etc still be helpful in autoimmunity but for different symptoms?

I always think about @Shawn case who was helped by Rituximab for autoimmunity (like me) even though we had different autoantibodies and different symptoms?

Of course, yes. But I was actually trying to say that I am afraid that my classical ME with PEM and physical fatigue etc, comes from something else, while CellTrend antibodies perhaps make my POTS or even possibly AE, because my cognitive symptoms are out of the common ME range, likely it's PANDAS or unknown Autoimmune Encephalitis.

Wouldnt Fluge & Mella study find this subgroup, and obviously they havent, not published yet, but we cant expect they have.. that's what the message was. Shouldnt on CellTrend positive subgroup Rituximab be more effective?!
It'd be best news in 2018 for me if it turns out so.

Shawn had anti-NMDAR, that's confirmed AE. I dont see myself that lucky for now

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But I was actually trying to say that I am afraid that my classical ME with PEM and physical fatigue etc, comes from something else, while CellTrend antibodies perhaps make my POTS or even possibly AE, because my cognitive symptoms are out of the common ME range, likely it's PANDAS or unknown Autoimmune Encephalitis.

I honestly don't know and each person's case is so unique when I learn more details. I just know that you have a lot of random autoantibodies (like me) which do not clearly match with one distinct disease. I have no idea what percent of your symptoms come from the autoantibodies and what percent from classic ME (or if there will someday be an autoantibody group within ME). I feel like we almost know nothing at this point in time which is kind of scary (I mean in general, I don't mean re: your case)!

Wouldnt Fluge & Mella study find this subgroup, and obviously they havent, not published yet, but we cant expect they have.. that's what the message was. Shouldnt on CellTrend positive subgroup Rituximab be more effective?! It'd be best news in 2018 for me if it turns out so.

I cannot remember how many subjects were in Fluge & Mella's study or exactly how they were selected. But I suspect if there was a study with people who are highly positive on the Cell Trend Autoantibodies like we are (me 7/9 and you 8/9) plus other autoantibodies and they were given high dose IVIG and Ritux over a long period of time, compared to a control group (however this would work, I guess they would get saline or dextrose?), I think we would learn something interesting from the results.

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I agree that would be really interesting and I think it would allow the "autoantibody group" to be studied separately in case they are confounding the research from the "classic ME" patients (for lack of better labels)!

I dearly hope other researchers are looking for these antibodies. We need validation from other research groups. I remember some time ago Suzanne Vernon tried to get a grant for a grand autoantibody study - she got buy-in from researchers across the U.S. - a very impressive group - but was, alas , turned down. Now maybe things will be different.

Senior Member

I cannot remember how many subjects were in Fluge & Mella's study or exactly how they were selected. But I suspect if there was a study with people who are highly positive on the Cell Trend Autoantibodies like we are (me 7/9 and you 8/9) plus other autoantibodies and they were given high dose IVIG and Ritux over a long period of time, compared to a control group (however this would work, I guess they would get saline or dextrose?), I think we would learn something interesting from the results.

there was approx 150 people. And I think they're keeping track of CellTrend autoantibodies, so if they've found connection we would know it, I am afraid.

As for very high positive numbers of antibodies, 7 or 8, the test is ELISA and it's to outer and inner surface proteins so there's a lot crossreactivity because all of these receptors are having many overlaps in protein chains sequences. Paolo is analysing this in the program he has built, so we'll know soon more... For now he was looking at M3 and M4 positive, + M1 negative patients, because those are most common ones, he said.

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btw Ginger, yes, I now think I understand even better what you meant... among 150 people there is hardly 2 people, max 3, with so high scores on CellTrend like you and me, and 2 other people on this forum. So, we might be even more specific autoimmune subgroup.

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Hi Pibee, I'm at IVIG do this will be brief but wanted to try to explain my thoughts further. There seems to be an "autoimmune group" of us not just with high Cell Trend Abs but usually also a positive ANA Titer and a bunch of other random Auto-Abs.

I think many people have not had the opportunity to even test for these Abs, so I suspect the group of people is even higher than we know.

Having said that, it seems there are only two options re: ME/CFS and this autoimmune group. The first is that they are an autoimmune sub-set of ME/CFS and the second is that they are a separate disease (s).

If they are a second disease(s) then figuring this out and taking them out of the research benefits everyone b/c it could discover a new disease AND it could stop confounding research like possibly the Ritux study (even it was just a handful of people like you said).

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For me personally doesnt make sense because I have the most classical ME you can imagine (along with many comorbid disorders like PANDAS).

but I dont know

Yes, most didnt test for CellTrend but I looked at Loebel et al (2016) and among 268 patients I found for many antibodies only 2 or 3 with higher scores than mine, so I assume it's quite rare, but we cant know the numbers. If only 29.5% are positive for M3 or M4 or B2, this would make it unlikely more than 5% are positive for 7-8.